2. The problem in defining requirements

At the meeting of the FAO/WHO Expert Committee on Protein
Requirements in 1963 (FAO/WHO, 1965) I maintained that there was only one level
of requirement worth talking about - the minimal requirement. I am now persuaded
that that view is too restricted because it was confined to results obtained by
nitrogen balance. Further, it was suggested that the requirements of all men are
more or less equal, to which a committee member from former Czechoslovakia
replied 'I am not so sure'. Nicol & Phillips wrote in 1976: 'The protein
requirements of all apparently healthy men can only be established in the
context of their ecological, socioeconomic and nutritional backgrounds'. Thus as
long as 30 years ago doubts were being expressed about the way in which protein
requirements should be formulated.

Millward said 'The established perception of the nature of protein
requirements is inadequate' (Millward et al, 1990). For him there are
three levels of requirement: the optimal, the operational and the minimal. The
optimal requirement would be determined by functional criteria such as good
health, growth, resistance to disease. These criteria are hard to define,
although studies of immune status could be used at the population level.
Chittenden lived a healthy and active life for many years on a protein intake of
about 30 g per day. He maintained that the high protein intakes recommended by
Voit (about 120 g per day) constituted 'individual and racial suicide'. This is
the only example I know of in which health has been the criterion for
recommending a specific level of protein intake.* It is an important task for
the future to search for correlations between protein intake and functional
criteria that can be stated in quantitative terms. For example, there is
increasing evidence that linear growth in children may be influenced by diets
that provide good quality protein (Allen, 1994; Golden, 1994), although we do
not know whether the effect is due to vitamins, minerals or amino acids. Golden
(1994) has put forward a convincing hypothesis for the role of sulphur amino
acids.

* Chittenden observed that in soldiers and athletes who had been
living on a generally high protein diet, change to a mainly vegetarian diet
providing 0.75 g protein/kg/d for 5 months led to an increase of 38% in strength
and work performance by 15 tests (Millward, 1994).

The operational requirement, a term introduced by Millward,
although it has overtones of the NPUop of Miller & Payne (1961),
will be discussed below in relation to the Millward-Rivers model. It takes
account of the fact that nitrogen balance can be achieved over a wide range of
protein intakes. This has long been recognized, at least since the time of Folin
(1905), but I think it is fair to say that we still do not know how this balance
is achieved (Waterlow, 1994).

The minimal requirement, which has been the object of innumerable
measurements, is, as its name implies, the lowest level of protein or amino acid
intake at which N balance can be achieved and maintained. The work of Sukhatme
& Margen (1978), which at one time had a good deal of influence, seemed to
imply that this minimal level could be variable in an individual. Millward et
al (1989) have said that their work implies 'a regulatory mechanism which
adjusts daily N balance over a period of several days ... adaptive mechanisms
exist which adjust output to balance intake and limit the extent of any loss or
gain of body protein. This is an alternative model defining the requirement as a
range of intakes over which equilibrium can occur. In contrast, the conventional
model is based on an intrinsic requirement which is a fixed function of body
weight'.

It is necessary to comment on this statement. The range of intakes
over which balance can be achieved is well recognized and the description of an
'alternative model' is unjustified. Sukhatme & Margen's theory of regulation
is based on the finding of auto-correlation in urinary N output. This means that
if the output on day 2 is lower than on day 1, it will be lower on day 3 than on
day 2, and so on. This process would, if continued, lead to zero output
(negative correlation) or infinite output (positive correlation). Obviously this
does not Occur; after a few days the cycle is reversed. This reversal appears to
be caused by random variation (Sukhatme, personal communication). Healy (1989)
has criticized the concept of autocorrelation on theoretical grounds; Rand et
al (1979) looked for it in a large series of long-term balance studies and
found evidence of it in only a small minority. In any case, autocorrelation, if
it relies on random variation to maintain a long-term steady state, would seem
to be the reverse of a regulatory mechanism. A regulatory mechanism is one
which, like a thermostat, manages to maintain a steady state by opposing or
reducing the effect of random variations or imposed fluctuations (Waterlow,
1985).

In the statement that 'the conventional model is based on an
intrinsic requirement which is a fixed function of body weight', the key words
are 'intrinsic' and 'fixed'. All balance studies are conducted on a particular
individual at a particular point in time with a particular body weight and total
body nitrogen. It seems reasonable to suppose on physiological grounds that the
nitrogen losses, which have to be balanced by the requirement, should depend on
the body weight, or better, the lean body mass or total body N. However, I know
of no studies that have attempted to establish how strong the correlation is, in
the way that we have studies relating the BMR to body weight or lean body mass.
I find it difficult to believe that such a correlation does not exist, but that
in no way rules out the influence of other factors, such as body composition,
age, sex and possibly height in relation to weight. For example, Egun &
Atinmo (1993) showed that on a Nigerian diet women had a lower protein
requirement per kg than men, but it was the same when related to lean body mass.
If the measurement of nitrogen balance was as easy as that of BMR, we would be
far further.

We have no information about whether the minimum requirement per
unit body nitrogen is in fact fixed. Studies in third world countries, where
people might be supposed to be existing on low protein intakes, have so far
shown no significant differences in obligatory N losses from those found in
industrialized countries (Torun et al, 1981; FAO/WHO/UNU, 1985). However,
even if there is a strict physiological relationship between the daily
obligatory losses and the amount of body N. there is still a possibility for
adaptation in the efficiency with which amino acids are used (Nicol &
Phillips, 1976). Millward (1992) contends that in the adult there is a set-point
for the upper limit of body protein, which is determined by height and frame
size. This idea of a set-point seems very reasonable. For example, in the normal
adult neither plasma albumin nor haemoglobin concentration can be raised above a
certain level by an increase in dietary protein. In experiments with rats, Henry
et al (1953) showed that with increasing protein intake total liver
protein rose towards an asymptote, with ever diminishing returns on the
increased intake.

It is also well recognized that on moving from a higher to a lower
protein intake there is a small loss of body protein, about 1% in the human
adult (Young et al, 1968). This small loss can apparently be tolerated
without harmful effects (Waterlow, 1985). It has been regarded as drawing on
'labile protein stores', but the concept of a store is inappropriate. It is
probably better to regard it as a kinetic adjustment that allows constancy of
body protein to be maintained at a new setting, the processes of protein
synthesis and breakdown needing a little time to adjust to the new level of
intake (Waterlow et al, 1978).

There is a further stage of adaptation. If the intake is too low
there will be an exponential loss of body protein until balance is achieved at a
new level of body weight (Waterlow, 1985). For example, if the requirement for
maintenance is taken as 0.1 g N per kg per day, and a 70 kg man is on a diet
that provides 5 g N, or 0.07 g per kg, other things being equal he will lose
body N until his weight has fallen to 50 kg, when he will again be in balance.
Of course, other things may not be equal; nitrogen may be used more efficiently,
as suggested by Allison's work on dogs (Allison, 1951). One may ask, what degree
of loss of body N is acceptable? If the subject initially had a height of 1.75 m
and at 70 kg a body mass index (BMI) of 22.8, at the end of this second stage
the BMI would be 16.3, which, according to current thinking, would be
inacceptable (James et al, 1988). Moreover, it appears that such a loss
would not be uniform, but would involve a disproportionate amount of muscle
mass, visceral mass being well maintained (Soares et al, 1991). This is a
further reason why the nitrogen balance at a given point in time cannot be
regarded as giving a complete answer to the question of the protein requirement.
If we regard the requirement per unit body weight as fixed, what is the ideal
body weight at which it should be fixed, or is anything short of Millward's
setpoint
suboptimal?